title: Synthesis, cytotoxicity and DNA binding of oxoazabenzo[de]anthracenes derivatives in colon cancer Caco-2 cells.
abstract: New oxoazabenzo[de]anthracenes derivatives were synthesised and characterised. Their interactions with calf thymus DNA were studied by UV spectrophotometric analysis and a competitive ethidium bromide displacement assay. Cytotoxicity was determined by MTT assay, against colon adenocarcinoma (Caco-2 cells). Among all the oxoazabenzo[de]anthracenes derivatives reported herein only the piperidino derivative exhibited strong DNA binding properties and cytotoxic activity with IC₅₀ values in the range of 16 ± 1.5 μM (72-h treatment). In addition, the piperidino derivative did not directly inhibit topoisomerase I and topoisomerase II enzymes. The results confirm that the presence of the oxoazabenzo[de]anthracenes together with the piperidino functionality is crucial in exerting DNA binding and cytotoxic properties, hence demonstrating promise as a chemical scaffold for further development of new anticancer agents.
authors.affiliation: Institute for Health & Welfare Research, School of Pharmacy & Life Sciences, Robert Gordon University, Riverside East, Garthdee Road, Aberdeen AB10 7GJ, Scotland, UK. Electronic address: a.di-salvo@rgu.ac.uk.
authors.forename: Alberto
authors.initials: A
authors.lastname: Di Salvo
authors.forename: Pauline
authors.initials: P
authors.lastname: Dugois
authors.forename: Delphine
authors.initials: D
authors.lastname: Tandeo
authors.forename: Marie
authors.initials: M
authors.lastname: Peltekian
authors.forename: Paul
authors.initials: P
authors.lastname: Kong Thoo Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D018938:Caco-2 Cells; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D048588:Benzoxazines; D006576:Heterocyclic Compounds, 4 or More Rings; D004247:DNA; C427203:calf thymus DNA
keywords: Anthraquinone derivatives; Anticancer; Cytotoxicity; DNA-binding; Synthesis